Abstract Established in January 2003, the mission of the NCMHD Center of Excellence in Nutritional Genomics, a collaborative program between UCD and Children's Hospital Oakland Research Institute, is to reduce and ultimately eliminate racial and ethnic health disparities resulting from gene x environment interactions, particularly those involving genetic, dietary, economic, and cultural factors. Our goal is to devise genome-based dietary interventions to prevent, delay, and treat diseases such as Type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), prostate cancer and asthma. To achieve this goal, the Center is taking an interdisciplinary approach to develop culturally competent methods and novel technologies to elucidate the complex interactions between environmental triggers, genes, and disease. Using a multiorganizational structure and a translational research approach, the Center will investigate the influence of diet and individual genetic variation as risk factors for health disparities in racial/ethnic populations in the U.S. Although certain genotypes are more severely affected by specific types of dietary factors than other genotypes, no genotype is completely immune to the deleterious effects of poor diet. We are using various genomic/informatic technologies to identify and characterize genes regulated by naturally occurring constituents in foods and those gene-subsets that influence the balance between health and disease. Such knowledge is necessary, but not sufficient, to address health disparities among racial/ethnic populations and the poor. Social, economic and cultural factors also come into play when selecting foods and when designing studies to identify causative genes and environmental factors. The specific objectives of the Center include: (1) Developing better approaches for human association studies that recognize the importance of population stratification in racially/ethnically mixed populations; (2) Integrating and translating genetic, genpmic, clinical and pathological information into medical insights that can be used to improve the quality of patient care; (3) Educating students, health care professionals and biomedical researchers about the biological and non-biological factors contributing to health disparities; (4) Establishing community engagement programs to inform health disparity communities about the importance of good nutrition and its relationship to genetic variation and ancestral background. The focus of this competitive renewal application is on research projects that will generate new knowledge and insights into the biologic factors contributing to health disparities. Our proposal includes nutritional genomic studies that will reduce health disparities by providing clinicians, physicians and public health professionals a better understanding of how environmental factors can influence the complex interactions between phenotype and genotype.